Letter to the Editor
Evolocumab for the treatment of heterozygous familial hypercholesterolaemia in end-stage chronic kidney disease and dialysis
Evolocumab para el tratamiento de la hipercolesterolemia familiar heterocigota en enfermedad renal crónica avanzada y diálisis
Silvia González Sanchidrián
, Pedro Jesús Labrador Gómez, José Carlos Aguilar Aguilar, Elena Davin Carrero, Sandra Gallego Domínguez, Juan Ramón Gómez-Martino Arroyo
Corresponding author
Servicio de Nefrología, Hospital San Pedro de Alcántara, Complejo Hospitalario Universitario de Cáceres, Cáceres, Spain
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Although the diagnosis is usually clinical and/or by laboratory tests, genetic testing is necessary for a definitive diagnosis.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">1,2</span></a> It is transmitted in an autosomal dominant manner and the most common cause is genetic mutation of LDL receptors (LDLR); less common are mutations in the apolipoprotein B100 gene (apo-B100) or proprotein convertase subtilisin/kexin type 9 (PCSK9).<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Two monoclonal antibodies which are inhibitors of PCSK9 have recently been approved (evolocumab: Repatha<span class="elsevierStyleSup">®</span> and alirocumab: Praluent<span class="elsevierStyleSup">®</span>) for the control of dyslipidaemia in high-risk patients in whom a sufficient reduction of LDL-C is not achieved with the usual lipid-lowering therapies.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Evolocumab has been authorised for adult patients with primary hypercholesterolaemia (familial heterozygous and non-familial), mixed dyslipidaemia or established atherosclerotic cardiovascular disease, as a complement to the diet: (1) in combination with a statin or with a statin and other lipid-lowering therapies in patients who do not achieve target levels of LDL-C with the maximum tolerated dose of statin; or (2) alone or in combination with other lipid-lowering therapies in patients intolerant to statins or in whom statins are contraindicated; and for patients from 12 years of age with homozygous FH in combination with other lipid-lowering therapies.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">We present the case of a 33-year-old male with a history of obesity, hyperuricaemia and acute myocardial infarction at the age of 25, with angioplasty and stent implantation in the anterior descending coronary artery.</p><p id="par0030" class="elsevierStylePara elsevierViewall">After the cardiac event and the finding of elevated LDL-C (>160<span class="elsevierStyleHsp" style=""></span>mg/dl), treatment was started with rosuvastatin 20<span class="elsevierStyleHsp" style=""></span>mg/day and ezetimibe 10<span class="elsevierStyleHsp" style=""></span>mg/day. Genetic testing located a mutation in the LDLR gene, confirming the diagnosis of heterozygous FH, (mutation M079, genetic identification c.1342C>T, protein identification p.GIn427X).</p><p id="par0035" class="elsevierStylePara elsevierViewall">In 2011, at the age of 27, he was referred to nephrology with proteinuria (0.5<span class="elsevierStyleHsp" style=""></span>g/day) and microhaematuria. After two years of follow-up, due to persistence of proteinuria (0.8<span class="elsevierStyleHsp" style=""></span>g/day), microhaematuria and deterioration in renal function (creatinine 1.42<span class="elsevierStyleHsp" style=""></span>mg/dl), estimated glomerular filtration rate (eGFR) by CKD-EPI 66<span class="elsevierStyleHsp" style=""></span>ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>, we suggested to perform a renal biopsy, but the patient rejected the idea and discontinued the nephrology follow-up visits.</p><p id="par0040" class="elsevierStylePara elsevierViewall">In 2016, due to poor control of LDL-C he was started on evolocumab (140<span class="elsevierStyleHsp" style=""></span>mg/15 days), and achieved optimal control of his LDL-C levels.</p><p id="par0045" class="elsevierStylePara elsevierViewall">A year later he was referred once again to nephrology with creatinine 4.22<span class="elsevierStyleHsp" style=""></span>mg/dl and eGFR CKD-EPI 17<span class="elsevierStyleHsp" style=""></span>ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>. Given the rapid progression of the renal failure (RF), although probably due to the natural evolution of his kidney disease, it was decided to withdraw evolocumab after 12 months of treatment because it was not tested in patients with end-stage kidney disease. The patient's LDL-C levels then climbed, despite treatment with rosuvastatin and ezetimibe. In view of the patient's high cardiovascular risk because of the FH and kidney disease, after six months it was decided to restart evolocumab at the same dose, while continuing rosuvastatin and ezetimibe. The patient started the peritoneal dialysis programme in 2018, maintaining adequate lipid control and without evidence of adverse effects attributable to the monoclonal antibody. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the changes in the lipid profile and renal function before and after treatment with evolocumab.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">The safety and tolerability of evolocumab was tested for patients with hypercholesterolaemia in the OSLER study.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a> However, patients with severe RF (eGFR<span class="elsevierStyleHsp" style=""></span><30<span class="elsevierStyleHsp" style=""></span>ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>) have not been studied in phase <span class="elsevierStyleSmallCaps">ii</span> and <span class="elsevierStyleSmallCaps">iii</span> trials.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a> No dose adjustment is necessary in patients with mild or moderate RF.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">7</span></a> In phase <span class="elsevierStyleSmallCaps">i</span> the pharmacokinetic and pharmacodynamic results showed that the average evolocumab exposure was lower in patients with severe RF or on haemodialysis compared to subjects without RF.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">7</span></a> The safety data were similar between groups and no clinically significant difference in LDL-C was found.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">4,7</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Despite its high prevalence, FH remains an underdiagnosed and undertreated disease.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> Screening and early diagnosis are necessary for an adequate stratification of cardiovascular risk and effective treatment before the onset of major events.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">There is a real lack of consensus in the clinical guidelines for the management of dyslipidaemia in the renal patient,<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">8</span></a> but there are several studies which support the innocuous nature of LDL-C reduction to figures below the current recommendations.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">9</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">In our experience, evolocumab has proved to be an effective and safe option for the dislipemia treatment of a patient with FH with advance chronic kidney disease and on peritoneal dialysis.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: González Sanchidrián S, Labrador Gómez PJ, Aguilar Aguilar JC, Davin Carrero E, Gallego Domínguez S, Gómez-Martino Arroyo JR. Evolocumab para el tratamiento de la hipercolesterolemia familiar heterocigota en enfermedad renal crónica avanzada y diálisis. Nefrologia. 2019;39:218–220.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">eGFR: estimated glomerular filtration rate; HDL-C: HDL cholesterol; iPCSK9: proprotein convertase subtilisin/kexin type 9 inhibitor; LDL-C: LDL cholesterol; Lp(a): lipoprotein(a); TG: triglycerides; TotChol: total cholesterol.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">2011 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">2013 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">Feb/16 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">Jun/16 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">Oct/16 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">Feb/17 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">May/17 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">Aug/17 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">Nov/17 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">Jan/18 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">Mar/18 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">May/18 \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Treatment with iPCSK9 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="4" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Evolocumab</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">No treatment</th><th class="td" title="table-head " colspan="4" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Evolocumab</th></tr><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Renal replacement therapy \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Peritoneal dialysis</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Creatinine (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.81 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">eGFR CKD-EPI (ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TotChol; mg/dl \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">239 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">260 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">199 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">120 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">146 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">115 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">152 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">163 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">112 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">117 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LDL-C (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">162 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">185 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">129 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">103 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HDL-C (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TG (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">140 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">142 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">127 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">102 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">159 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">110 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">114 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">113 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">101 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">104 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">90 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lp(a) (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2018713.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Lipid profile in a patient with heterozygous familial hypercholesterolaemia and chronic kidney disease over the course of the disease according to treatment with evolocumab.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0050" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Familial hypercholesterolaemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J.C. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 7 | 8 | 15 |
| 2024 October | 40 | 31 | 71 |
| 2024 September | 49 | 28 | 77 |
| 2024 August | 73 | 86 | 159 |
| 2024 July | 47 | 41 | 88 |
| 2024 June | 57 | 49 | 106 |
| 2024 May | 60 | 44 | 104 |
| 2024 April | 51 | 51 | 102 |
| 2024 March | 45 | 25 | 70 |
| 2024 February | 33 | 33 | 66 |
| 2024 January | 42 | 41 | 83 |
| 2023 December | 38 | 38 | 76 |
| 2023 November | 43 | 42 | 85 |
| 2023 October | 31 | 24 | 55 |
| 2023 September | 43 | 39 | 82 |
| 2023 August | 35 | 23 | 58 |
| 2023 July | 46 | 30 | 76 |
| 2023 June | 41 | 33 | 74 |
| 2023 May | 49 | 36 | 85 |
| 2023 April | 35 | 20 | 55 |
| 2023 March | 43 | 24 | 67 |
| 2023 February | 43 | 17 | 60 |
| 2023 January | 39 | 31 | 70 |
| 2022 December | 45 | 33 | 78 |
| 2022 November | 65 | 32 | 97 |
| 2022 October | 51 | 50 | 101 |
| 2022 September | 37 | 35 | 72 |
| 2022 August | 35 | 37 | 72 |
| 2022 July | 36 | 42 | 78 |
| 2022 June | 38 | 32 | 70 |
| 2022 May | 44 | 32 | 76 |
| 2022 April | 72 | 60 | 132 |
| 2022 March | 44 | 54 | 98 |
| 2022 February | 56 | 86 | 142 |
| 2022 January | 55 | 36 | 91 |
| 2021 December | 86 | 55 | 141 |
| 2021 November | 82 | 38 | 120 |
| 2021 October | 101 | 42 | 143 |
| 2021 September | 46 | 32 | 78 |
| 2021 August | 67 | 36 | 103 |
| 2021 July | 50 | 29 | 79 |
| 2021 June | 62 | 29 | 91 |
| 2021 May | 69 | 60 | 129 |
| 2021 April | 127 | 72 | 199 |
| 2021 March | 64 | 46 | 110 |
| 2021 February | 37 | 26 | 63 |
| 2021 January | 42 | 18 | 60 |
| 2020 December | 61 | 19 | 80 |
| 2020 November | 43 | 22 | 65 |
| 2020 October | 39 | 33 | 72 |
| 2020 September | 39 | 14 | 53 |
| 2020 August | 34 | 28 | 62 |
| 2020 July | 40 | 7 | 47 |
| 2020 June | 47 | 22 | 69 |
| 2020 May | 58 | 19 | 77 |
| 2020 April | 46 | 18 | 64 |
| 2020 March | 41 | 7 | 48 |
| 2020 February | 74 | 41 | 115 |
| 2020 January | 104 | 44 | 148 |
| 2019 December | 64 | 22 | 86 |
| 2019 November | 55 | 24 | 79 |
| 2019 October | 74 | 13 | 87 |
| 2019 September | 49 | 16 | 65 |
| 2019 August | 91 | 22 | 113 |
| 2019 July | 39 | 35 | 74 |
| 2019 June | 42 | 32 | 74 |
| 2019 May | 41 | 31 | 72 |
| 2019 April | 100 | 56 | 156 |
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